TCR stimulation of naive CD4 T-cells in the presence of IL-4 leads to the differentiation of type 2 T helper (Th2) cells. An experimental system will be developed to determine the roles of the transcription factor GATA-3 in the establishment and maintenance of Th2 cells. The investigator aims to identify additional transcription factors that are also critical to the differentiation process. In addition, DNA-protein interactions involving GATA-3 and Stat6 will be studied. The ultimate goal of the research project is to provide a clear understanding of the molecular pathways that lead to the differentiation and functional activation of Th2 cells. It is proposed that knowledge gained from these studies will advance understanding and improve treatment of immunological diseases such as allergy and infection where Th2 responses are critical.